Project Summary (Project 4, Co-PIs: Lin, Froemke, Buzsaki, Tsien) Social bonding refers to an intimate relationship formed among members of the same species. Across species, social bonding is often accompanied by increased aggressiveness towards perceived threats against the object of attachment. The neural process underlying the social bonding induced increase in aggression remains unclear. Oxytocin plays pivotal roles in the formation of social bonds. Coincidently, the ventrolateral part of the ventromedial hypothalamus (VMHvl), a hypothalamic region indispensable for both male and female aggression expresses high level of oxytocin receptor and a dense cluster of oxytocin neurons are found right next to the VMHvl. Thus, we hypothesize that oxytocin may play an important role in altering the VMHvl cell responses to potential threat to increase female aggression after mother-infant bonding. Here we will test this hypothesis through three aims. In Aim 1, we will test the functional role of local and distal oxytocin inputs to the VMHvl in increasing female aggression during lactation. In Aim 2, we will perform in vivo cell-type specific recording to address how VMHvl cells and their neighboring oxytocin neurons respond during natural female aggression. Additionally, we will employ a novel genetically encoded oxytocin sensor to address how oxytocin influences the activity of VMHvl cells in nave and lactating females. In Aim 3, we will employ RNAseq and in vitro slice recording to investigate how the VMHvl cells change the molecular and electrophysiological properties during lactation. In summary, this project will combine the various tools developed in Projects 1-3 to provide new insight into the neuromodulatory mechanisms in hypothalamus that alter aggressive behavior during social bonding.